The principal objective of the Biophysical Imaging Core is to provide Program investigators with a complete range of expertise, training, equipments, and data analysis tools to obtain nano-to-micro scale biophysical information pertaining to the cellular and molecular basis of endothelial barrier permeability. Core D personnel and equipment will allow PPG scientists to image 3D structures, evaluate physical and chemical properties and define perturbant-induced real-time changes in the structures and activity of cells and subcellular constituents, including membranes, cytoskeletal networks and cell-matrix and cell-cell junctions. This Biolmaging Core supports the PPG's five research projects with quantitative microscopy related to atomic force microscopy (AFM), light fluorescence microscopy and TIRF (total internal reflection fluorescence microscopy). It offers access to experienced use of the complete resources of the Center for Nanomedicine that includes state-of-the-art atomic force microscopes integrated with high resolution single photon microscopy and fluorescence microscopy systems for simultaneous multimodal correlative studies. In addition, this Core will also make use of the common resources available at the University of Chicago IBD (Institute for Biophysical Dynamics) Microscope Facility (which includes an excellent electron microscope facility) and the Department of Medicine's Multiphoton Laser Scanning Microscope Facility. Led by Core Leader Ratnesh Lai, PhD, the core has assembled the personnel and laboratory facilities to satisfy a wide range of experimental 3D imaging and mechanobiophysics needs. Core D personnel have professional experience spanning the fields of high resolution imaging and examining physical and chemical properties, including mechanobiophysics with various scanning probe microscopies. Despite relative recent arrival of Core personnel within the University of Chicago, these talented scientists have provided convincing preliminary data for each Project and all five research projects.